During his time there, he also oversaw a number of important first team signings and developed partnerships with junior and amateur clubs, locally, nationally and internationally.

In 2005, Comolli became director of football at Tottenham Hotspur, with overall responsibility for the medical, academy, scouting and club secretarial departments, replacing the outgoing Frank Arnesen.

[5] During his time there, he had several disagreements with first-team head coach Martin Jol, who, after his departure from Spurs, complained several players had been signed by Comolli without his agreement and that they had left the squad "unbalanced".

[6][7] Comolli spent three years in the job but with Tottenham performing poorly in 2008–09 and some of Comolli's signings coming in for criticism,[8] he was dismissed in October 2008, shortly after the dismissals of manager Juande Ramos, assistant Gus Poyet and first team coach Marcos Álvarez, as the director of football position was abolished at the insistence of incoming manager Harry Redknapp.

[10] Comolli was also responsible for the signings of former Tottenham first-team squad members Luka Modrić, Benoît Assou-Ekotto, Heurelho Gomes, David Bentley, Vedran Ćorluka and Roman Pavlyuchenko, as well as Dimitar Berbatov.

[18][19] In the summer transfer window for the 2011–12 season, Comolli helped Liverpool sign Jordan Henderson, Charlie Adam, Stewart Downing, Doni, José Enrique, Sebastián Coates and Craig Bellamy.

[21] Comolli made an instant impact at Fenerbahçe as he was responsible for the signings of Islam Slimani, André Ayew and Victor Moses for 2018-19 season.